The primary objective of this project is to develop an female mouse model for studying gonococcal (GC) pathogenesis of the female reproductive tract, and for evaluating GC vaccines. Results obtained in the first five months of this project include the successful colonization of mice in the estrus phase. Both vaginal and uterine colonization were seen 24 hours post inoculation, suggesting dissemination to the upper reproductive tract had occurred. Longer duration of infection was perhaps inhibited by normal host factor changes which occur upon transition into the diestrus phase of the reproductive cycle. Future experiments will therefore use estradiol-treated mice to increase susceptibility to infection. Once this model is standardized, immunity to infection will be studied by challenging mice who have recovered from infection, the nature of the protective immune response will be explored. A particular emphasis will be placed on the in vivo expression of, and immune responses to, GC opacity proteins, based on epidemiological data which suggest that the presence of antibody to these proteins decreases the risk of salpingitis. Mice will be immunized with purified GC proteins and then challenged to see if protective antigens can be identified, including those that might not protect against colonization, but protect against dissemination to the upper reproductive tract.